Radioactive barium-137

ABSTRACT

Radioactive barium-137m is obtained by eluting a generator comprised of the parent isotope, cesium-137, on a cobalt (II) ferrocyanide substrate.

United fiafies P010111 1151 3,663,177

Arino et a1. 1451 May 16, 1972 [5 RADIQACTIVE BARIUM-l37 Reierences Cited [72] inventors: Hirofumi Arino, Suffern; Vincent D. Rear- UNITED STATES PATENTS Han/Straw, NY 3,156,532 1 1/1964 Doering et a1. 23/252 [73] Assignee: Union Carbide Corporation, New York, 3,345,305 10/1967 30min 6! 52/30l.l N.Y. 3,450,640 6/1969 Bonnin et al... ....252/30l.l 3,453,214 7/1969 Bonnin 6! al ..252/30l.1

[22] Filed: Aug. 28, 1968 [21] App]. No.: 755,820 Primary Examiner-Benjamin R. Padgett AttorneyPaul A. Rose, Gerald R. OBrien, Charles J. Metz and William R. Moran [52] U.S. Cl. ..23/252 R, 23/31 1, 23/312, 250/106 S, 252/301. 1, 424/1 51 1m. 01 ..B0ld 59/30, A6lk 27/04,c091 3/00 [571 ABSTRAQT [58] Field Of Search ..424/l; 21 l, 212; Radioactive barium l 7 is obtained y eluting a generator 252/3011; 250/106 comprised of the parent isotope, cesium-137, on a cobalt (ll) ferrocyanide substrate.

7 Claims, No Drawings RADIOACTIVE BARIUM-l 37 This invention relates to a novel process for the production of radioactive barium-137m. In one aspect, this invention relates to a novel process for the production of radioactive barium-137m in high yields. A further aspect of this invention is directed to a novel process for the production of radioactive barium-137m which can be obtained in a high degree of purity.

Barium-137m, the daughter nuclide of cesium-137, is known to be an extremely convenient isotope for medical research and diagnosis. It is particularly suitable for the study of vascular dynamics, such as blood flow rates. Due to the relatively short half-life of 2.6 minutes, barium-137m can be safely administered in multicurie quantities with a very limited radiation dose. This is of particular importance when a clear, sharp scanning picture is desired. The short half-life of barium-l 37m also renders it of interest for educational purposes. For example, students can measure nuclear properties in a limited classroom period, using a non-shielded, low activity barium-137m generator. Barium-137m can also be used for various other purposes where a short half-life is desired.

Heretofore, various methods have been employed for the preparation of barium-137m generators. For example, J. J. Pinajian (J. Chem. Educ. 44, 212, 1967) adsorbed cesium-137 on zirconium phosphate and extracted barium-137m in 1M hydrochloric acid with a recovery of about 20 percent. M. Blau et a1. (Nucleonics 24,60, Oct. 1966) prepared a barium- 137m generator using a mixture of ammonium molybdophosphate and asbestos. About 50 percent of barium-137m was eluted with 0.1M hydrochloric acid. A. Bonnin et al. (French Pat. No. 1,392,506) used cupric ferrocyanide and recovered 12-20 percent barium-137m in barium nitrate solution. However, from these generators, barium-137m is not recoverable in physiological isotonic saline solution, water or dilute hydrochloric solution; thus, requiring the additional chemical treatment of the eluent for an intravenous injection into a human body or for other experiments. The additional chemical step is, of course, not desirable for barium-137m since it decays rapidly. Furthermore, prior to the instant invention the recovery of barium-137m from the known generators is poor.

It is therefore an object of this invention to provide a more efficient method for producing radioactive barium-137m. Another object of this invention is to provide a process for preparing radioactive barium-137m in a high degree of purity and by an extremely reproducible and simple process. An object of this invention is to produce radioactive barium-137m by a method wherein the degree of recovery is high. A further object of this invention is to provide a process for preparing radioactive barium-137m of a high degree of purity and which is acceptable for medical research and diagnosis. A still further object of this invention is to provide a sterile, physiological, saline solution containing radioactive barium- 137m. These and other objects will readily become apparent to those skilled in the art in the light of the teachings herein set forth.

It has now been discovered that the aforementioned objects can be achieved by a process which comprises the steps of (a) recovering cesium-137 from its reactor irradiated target, (b) contacting the cesium isotope with a cobalt (II) ferrocyanide, and (c) thereafter eluting the barium-137m from its parent isotope with a suitable eluting solution.

Radioactive barium-137m prepared by the process of this invention is obtained in a very high degree of purity and is therefore suitable for use in medical research and diagnosis. In contrast to the known methods, referred to above this process is extremely simple and rapid providing a high recovery of barium. Moreover, in contrast to the known methods, the eluted barium isotope is free of undesirable ions and organic agents. Additionally, since further chemical purification of the eluent is unnecessary, full advantage can be taken of the relatively short half-life of this isotope.

As hereinbefore indicated, barium-137m is obtained from its parent element cesium-137. The cesium-137 is commercially available and is obtained as the fission product of uranium. The irradiation of the uranium target material is a well known technique and can be effected by placing uranium in the irradiation zone of a nuclear reactor, particle generator or neutron isotopic source. Purification of the cesium-137 prior to its use in the instant process can also be effected by known chemical methods, thereafter, the cesium-137 is contacted with a cobalt (ll) ferrocyanide, from which the daughter isotope, barium-137m can be eluted. The cobalt ferrocyanides which have been found to be useful in the present invention, are those having the formula:

wherein M represents nickel, zinc, iron (11) and copper (II). The copper (II) cobalt ferrocyanide is the preferred substrate for the cesium-137.

A generator containing the cesium-137 can be conveniently prepared by contacting the cobalt ferrocyanide with the irradiated target materials and thereafter loading it onto a column.

In practice this can be done by dissolving the cesium-137 in a suitable solvent and contacting the resulting solution with the cobalt ferrocyanide. In order to minimize any cesium breakthrough in the barium-137m eluent, as would be necessary for pharmaceutical applications, it is essential that the cobalt ferrocyanide, on which is adsorbed the cesium-137 solution, be heated at a temperature of from about 50 C. to about 100 C. for a period of at least about 2 minutes. In those instances where the purity of the eluent is not essential, the heating step can be omitted. However, due to the relatively long half-life of the parent element, cesium-137, it is preferred to employ the heating step and avoid its presence in the eluent.

Although a variety of solvents, can be employed to load the cesium-137 onto the cobalt ferrocyanide, it is preferred to employ a slightly acidic, aqueous solution. Suitable solvents therefor include water, or an aqueous solution of an inorganic acid, such as 0.1M hydrochloric acid. Hydrochloric acid is particularly preferred since the resulting cesium breakthrough is minimized. For instance, when 0.1M nitric acid was employed the cesium breakthrough was found to be about 0.3 percent. However, when 0.1M hydrochloric acid was used, the breakthrough was reduced to about 0.01 percent.

It has also been observed that the recovery of barium-137m from the generator decreases with time from about percent to about 20 percent over a 2 month period. However, if a reducing agent such as graphite, carbon black, charcoal, and the like, is mixed with the cobalt ferrocyanide, the recovery of barium-137m remains as high as percent over the life of the generator. The reducing agent is usually employed in an amount of from about 5 to about 60 percent and more preferably from about 30 to 40 percent based on the weight of the cobalt ferrocyanide employed.

It has also been found that when the eluted barium-137m must be of a high degree of purity, a filter should be employed to prevent cesium-137 from contaminating the eluent. While a variety of filtering devices can be employed, it has been observed that any anion exchange such as hydrous zirconium oxide is ideally suited for this purpose. The anion exchanger can be placed in the generator below the ferrocyanide so as to filter any undesirable cesium-137.

Hence, in in preparing a barium-137m generator from which it is desired to obtain a highly pure eluent, it is essential to heat the loaded substrate, employ a reducing agent, and use filtering means to eliminate any traces of cesiuml 37. The purity of the barium-137m solutions obtained from such a generator is high, containing approximately 2 X 10 percent cesium-137, and less than 1 part per million of iron, cobalt, copper and cyanide ions.

As hereinbefore indicated, the process of this invention is suitable for the production of barium-137m for educational purposes. For such uses it is of course, not essential that the cesium-137 breakthrough be controlled, nor a reducing agent or filtering means be employed. However, for most purposes it will be preferred to employ these steps to maximize the life and efficiency of the generator.

After the substrate containing the cesium-137 is prepared it is then transferred to an appropriate elution system such as a column, or vessel, preferably glass, or other inert material. The system is washed with water and the supernatant liquid is allowed to drain or be removed by filtration or decantation. The substrate is then washed with isotonic saline and is ready for eluting.

As previously indicated, the process of the present invention provides a simple method for the preparation of barium- 137m in a high degree of efficiency. By this process recovery of barium-137m can be effected with isotonic saline in efficiencies as high as 90 and higher, without dissolution of the substrate or removal of any significant amounts of cesium from the substrate.

The following examples are illustrative:

EXAMPLE 1 This example illustrates the preparation of highly pure barium- 1 37m such as would be required for use as a medical diagnostic agent.

5 milliliters of percent potassium ferrocyanide solution and 0.5 milliliter of 1 molar hydrochloric acid were added to 3 grams of hydrous zirconium oxide (100-200 mesh). The slurry was mixed well, transferred into a column with an inside diameter of l centimeter with a glass frit. Then, 20 milliliters of a 1 percent cupric sulphate solution in 0.1 molar hydrochloric acid and 50 milliliter of water were successively passed through the column. The cupric ferrocyanide thus coated on hydrous zirconium oxide serves as the filter for cesium-137.

The main part of the generator, the cupric form of cobalt (II) ferrocyanide, which adsorbs Cs-137 and elutes barium 137m was prepared in the following manner. 10 milliliters of 10 percent cupric sulphate in 0.1 molar hydrochloric acid was added to 1 milliliter of a commercially available potassium cobalt (I1) ferrocyanide. The slurry was heated for 30 minutes at about 80 C. After cooling, the supernate was decanted and the solid phase was washed three times with water by decantations. To the cupric form of cobalt (II) ferrocyanide thus prepared, 1 millicurie of Cs- 1 37 in 0.1 molar hydrochloric acid was added. The slurry was heated for about 30 minutes at 85-90 C. and allowed to cool for another 30 minutes. Then, 0.4 grams of graphite particles (20-50 mesh) was added and mixed with the slurry. The mixture was transferred into the column containing the cesium-137 filter and the column was washed with 100 milliliters of physiological saline solution. Both ends of the column were sealed with rubber septums and aluminum crimp caps. One end of the generator was connected to a source of physiological saline solution and another end to a receiving bottle using a proper tubing and needles. A millipore filtering unit was attached to the tubing prior to the solution flowing into the receiving bottle. Ba-l37m was obtained in the receiving bottle by washing the column with physiological saline solution.

Table 1 shows the adsorptionelution characteristics of the Ba-l 37m generator.

TABLE 1 The Adsorption-Elution Characteristics of the Medical Ba- 1 37m Generator Cs-l 37 Adsorption Capacity: 0.7 meq per milliliter of the cupric form of hexacyano cobalt (11) ferrate (11) Recovery of Ba-137m in 10 milliliter of phsiological saline Total heavy metal: Cyanideion: Radiation Chemical Effect:

=1 part-per-million 0.5 part-per-million none EXAMPLE 2 This example illustrates the preparation of barium-137m wherein the isotope need not be highly pure as, for example, in educational or industrial applications.

A hundred microcurie of Cs-l37 activity was adsorbed on the cupric form of cobalt (11) ferrocyanide in the same manner as described earlier. Then, a small portion of the substrate containing 1 microcurie of Cs-137 was transferred onto a small sized filtering unit such as Swinex filtering unit manufactured by Millipore Corporation. The radioactivity was adjusted to a desired level by counting on a detector such as a gamma ray scintillation counter or G. M. counter. The filtering unit was then sealed, connected with a syringe containing an eluent, and eluted. Table II shows the elution characteristics of the generator. When physiological saline solution is used as the eluent, an occassional treatment with acid, for example once each 2 month period with 0.1 molar hydrochloric acid, is required to maintain a high Ba-137m recovery.

TABLE 11 The Elution Characteristics of the Educational or Industrial Ba-l37m Generator Recovery of Ba-l 37m in 5 milliliter of 0.1

molar hydrochloric acid: :10% Recovery of Ba-l37m in 5 milliliter of 0.1

molar nitric acid: 8511070 Recovery of Ba-137m in 5 milliliter of physiological saline solution: 85:Ll0% Recovery of Ba-l37m in 5 milliliter of water: 10-40% Cs-l37 breakthrough: ==0.0l% Total heavy metal: 10 part-per-million Cyanide ion: none Although the invention has been illustrated by the preceding example, it is not to be construed as being limited to the materials employed therein, but rather, the invention encompasses the generic area as hereinbefore disclosed. Various modifications and embodiments of this invention can be made without departing from the spirit and scope thereof.

What is claimed is:

l. A radioactive isotope generator comprised of, in combination,

a. an elutable substrate containing a cobalt ferrocyanide of the formula:

M [CoFe(CN) wherein M represents a member selected from the group consisting ofnickel, zinc, iron (11) and copper (II) and deposited therein cesium-137m,

b. means for supporting said substrate and c. entrance and exit means for eluting said substrate.

2. The radioactive isotope generator of claim 1 wherein said cobalt ferrocyanide is cupric cobalt (11) ferrocyanide.

3. The radioactive isotope generator of claim 1 wherein said 137. substrate contains a reducing agent.

4. The radioactive isotope generator of claim 3 wherein said reducing agent is charcoal.

5. The radioisotope generator of claim 1 wherein said sub- 5 strate is contained on a filter which selectively retains cesiumi 6. The radioisotope generator of claim 5 wherein said filter is hydrous zirconium oxide coated with cupric ferrocyanide.

7. A sterile radioactive isotope generator of claim 1. 

2. The radioactive isotope generator of claim 1 wherein said cobalt ferrocyanide is cupric cobalt (II) ferrocyanide.
 3. The radioactive isotope generator of claim 1 wherein said substrate contains a reducing agent.
 4. The radioactive isotope generator of claim 3 wherein said reducing agent is charcoal.
 5. The radioisotope generator of claim 1 wherein said substrate is contained on a filter which selectively retains cesium-137.
 6. The radioisotope generator of claim 5 wherein said filter is hydrous zirconium oxide coated with cupric ferrocyanide.
 7. A sterile radioactive isotope generator of claim
 1. 